Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1092 Chapter 20: Cancer
prospering at the expense of its neighbors. In the end—as the clone grows, evolves,
and spreads—it can destroy the entire cellular society (Movie 20.1).
In this section, we discuss the development of cancer as a microevolutionary
process that takes place within the course of a human life-span in a subpopulation
of cells in the body. But the process depends on the same principles of mutation
and natural selection that have driven the evolution of living organisms on Earth
for billions of years.
Cancer Cells Bypass Normal Proliferation Controls and Colonize
Other Tissues
Cancer cells are defined by two heritable properties: (1) they reproduce in defiance
of the normal restraints on cell growth and division, and (2) they invade
and colonize territories normally reserved for other cells. It is the combination of
these properties that makes cancers particularly dangerous. An abnormal cell that
grows (increases in mass) and proliferates (divides) out of control will give rise to
a tumor, or neoplasm—literally, a new growth. As long as the neoplastic cells have
not yet become invasive, however, the tumor is said to be benign. For most types
of such neoplasms, removing or destroying the mass locally usually achieves a
complete cure. A tumor is considered a true cancer if it is malignant; that is, when
its cells have acquired the ability to invade surrounding tissue. Invasiveness is an
essential characteristic of cancer cells. It allows them to break loose, enter blood
or lymphatic vessels, and form secondary tumors called metastases at other sites
in the body (Figure 20–1). In general, the more widely a cancer spreads, the harder
it becomes to eradicate. It is generally metastases that kill the cancer patient.
Cancers are traditionally classified according to the tissue and cell type from
which they arise. Carcinomas are cancers arising from epithelial cells, and they
are by far the most common cancers in humans. They account for about 80% of
cases, perhaps because most of the cell proliferation in adults occurs in epithelia.
In addition, epithelial tissues are the most likely to be exposed to the various
forms of physical and chemical damage that favor the development of cancer.
Sarcomas arise from connective tissue or muscle cells. Cancers that do not fit in
either of these two broad categories include the various leukemias and lymphomas,
derived from white blood cells and their precursors (hemopoietic cells), as
well as cancers derived from cells of the nervous system. Figure 20–2 shows the
types of cancers that are common in the United States, together with their incidence
and death rates. Each broad category has many subdivisions according to
the specific cell type, the location in the body, and the microscopic appearance of
the tumor.
In parallel with the set of names for malignant tumors, there is a related set of
names for benign tumors: an adenoma, for example, is a benign epithelial tumor
with a glandular organization; the corresponding type of malignant tumor is an
adenocarcinoma (Figure 20–3). Similarly, a chondroma and a chondrosarcoma
are, respectively, benign and malignant tumors of cartilage.
Most cancers have characteristics that reflect their origin. Thus, for example,
the cells of a basal-cell carcinoma, derived from a keratinocyte stem cell in the skin,
generally continue to synthesize cytokeratin intermediate filaments, whereas the
cells of a melanoma, derived from a pigment cell in the skin, will often (but not
always) continue to make pigment granules. Cancers originating from different
cell types are, in general, very different diseases. Basal-cell carcinomas of the skin,
for example, are only locally invasive and rarely metastasize, whereas melanomas
can become much more malignant and often form metastases. Basal-cell carcinomas
are readily cured by surgery or local irradiation, whereas malignant melanomas,
once they have metastasized widely, are usually fatal.
Later, we shall see that there is also a different way to classify cancers, one that
cuts across the traditional classification by site of origin: we can classify them in
terms of the mutations that make the tumor cells cancerous. The final section
of the chapter will show how this information can be crucial to the design and
choice of treatments.
Figure 20–1 Metastasis. Malignant tumors
typically give rise to metastases, making
the cancer hard to eradicate. Shown in
this fusion image is a whole-body scan of
a patient with metastatic non-Hodgkin’s
lymphoma (NHL). The background image
of the body’s tissues was obtained by CT
(computed x-ray tomography) scanning.
Overlaid on this image, a PET (positron
MBoC6 m20.01/20.01
emission tomography) scan reveals the
tumor tissue (yellow), detected by its
unusually high uptake of radioactively
labeled fluorodeoxyglucose (FDG). High
FDG uptake occurs in cells with unusually
active glucose uptake and metabolism,
which is a characteristic of cancer cells
(see Figure 20–12). The yellow spots
in the abdominal region reveal multiple
metastases. (Courtesy of S. Gambhir.)